1. Field of the Invention
The present invention relates to physiologically active peptides having cell death-preventing activity and/or cell growth-promoting activity, and to medium supplements for cell culture containing the same.
2. Background Art
In animal cells, changes in culture conditions are known to cause marked cell growth reduction and cell death. Accordingly, components derived from a mammal, such as fetal calf serum and bovine serum albumin, is generally added to a medium for animal cell culture to improve the efficiency of cell growth.
However, there has been pointed out that the components derived from a mammal may carry a risk of being contaminated with viruses, pathogenic agents, and the like, which could be a major problem in safety. Therefore, use of media without components derived from a mammal has been so far suggested. However, use of these media occasionally causes marked cell growth reduction and cell death, which makes the cell culture difficult.
Accordingly, a method of adding a peptide which is components derived from a plant and has cell growth-promoting activity, such as a peptide derived from wheat, in place of components derived from a mammal, to a medium for animal cell culture has been suggested for the purpose of promoting cell growth. However, even with use of such components derived from a plant, sufficient effect has not necessarily been attained for certain kinds of cells or under certain culture conditions.
Accordingly, the present inventors previously found that the protein sericin, which can be extracted from natural silkworm cocoons or the like, has growth-promoting activity for animal cells and thus suggested to add sericin to a medium (International Publication WO 02/086133). The sericin contained an essential region consisting of 38 amino acids and other nonessential regions. Further, a sericin derivative at least containing the essential region was also capable of exhibiting growth-promoting activity for animal cells. Such growth-promoting activity for animal cells was similarly exhibited with sericin or a sericin derivative which was artificially synthesized by a chemical or genetic engineering method.
However, there are several kinds of sericin components contained in natural silkworm cocoons and the like, even limiting to those with different molecular weight. Further, various classes of molecules are to be contained in a sericin fraction obtained by extraction since the process for sericin extraction comprises hydrolysis. In order to purify a single component having a specific structure from a mixture of such various classes of molecules, complicated operations and enormous costs are generally required. Further, such a mixture may not be appropriate for use in the field of pharmaceuticals or tissue engineering because its safety to the body or its stability is often difficult to be fully secured.
It is generally known that the larger the molecular weight of the peptide, the more complicated the structure, which causes technical difficulties in chemical synthesis and purification. From the viewpoint of obtaining a necessary amount of a highly purified peptide, it is desirable for the peptide to have a molecular weight as small as possible while retaining desired activity.
On the other hand, in the case where a peptide is produced using genetic engineering techniques, a complicated operation in which a gene coding for a target peptide is prepared and introduced into a host cell is required. In order to obtain the target peptide from the inside of cells or culture supernatant, many purification steps are required, which increases production costs.
In the fields such as the production of useful substances and tissue engineering by cell culture, there is still a great need for culture medium components which are highly safe, capable of improving cell growth efficiency, and obtainable by relatively inexpensive chemical synthesis.